What Causes Neurogenic Fever
Neurogenic fever is caused by neurological dysregulation of temperature control mechanisms, specifically from damage to the hypothalamus and its thermoregulatory pathways, occurring in the absence of infection or inflammatory processes. 1
Pathophysiological Mechanism
The fundamental cause is direct injury to hypothalamic structures that control temperature homeostasis. 2 This has been demonstrated using advanced neuroimaging:
- Diffusion tensor imaging (DTI) studies show structural damage to the hypothalamus in patients with neurogenic fever, with abnormal fractional anisotropy and apparent diffusion coefficient values indicating tissue injury 2
- The hypothalamus normally regulates temperature through homeostatic mechanisms controlling heat production, conservation, and heat loss 3
- When these regulatory centers are damaged, unregulated temperature elevation occurs without the typical inflammatory mediators seen in infectious fever 4
Specific Neurological Injuries That Cause Neurogenic Fever
Traumatic brain injury (TBI) is the most common cause, particularly with injuries affecting specific brain regions: 1
- Injuries rostral to vertebral level T4 are specifically associated with neurogenic fever development 5
- Hypothalamic injury (direct damage to temperature control centers) 2
- Injuries to the basal ganglia and medial temporal lobes 2
- Severe traumatic spinal cord injuries, especially at higher levels 5
Other neurological conditions that cause neurogenic fever include: 6
- Intracerebral hemorrhage, particularly pontine hemorrhage 7
- Intraventricular hemorrhage 2
- Brain neoplasms 6
- Ischemic stroke affecting temperature-regulating regions 1
Distinguishing Features from Other Fever Types
Neurogenic fever has specific characteristics that differentiate it from infectious or inflammatory causes: 8, 4
- Core temperature >37.5°C without evidence of sepsis or clinically significant inflammatory processes 1
- Persistent temperature elevations without cyclic patterns (unlike infectious fevers which often have diurnal variation) 8
- Absence of elevated inflammatory markers (normal white blood cell count, C-reactive protein, erythrocyte sedimentation rate) 2
- Often accompanied by other signs of autonomic dysregulation: tachycardia, paroxysmal hypertension, dilated pupils, tachypnea, and extensor posturing 6
Incidence and Clinical Context
Neurogenic fever is relatively common in traumatic brain injury, occurring in 4-37% of TBI survivors 9, though it was previously thought to be rare. The condition is more prevalent than historically recognized 1.
Critical caveat: Neurogenic fever is fundamentally a diagnosis of exclusion 4, 9. Patients with TBI are immunocompromised and predisposed to sepsis 9, making thorough infectious workup mandatory before attributing fever to neurogenic causes 4, 7.
Mechanism of Secondary Brain Injury
Once neurogenic fever develops, it causes harm through multiple mechanisms: 1
- Increased metabolic demands on already-injured brain tissue 1
- Enhanced release of excitatory neurotransmitters 1
- Increased free radical production 1
- Elevated intracranial pressure 1, 7
- Reduced tissue oxygen availability 5
- Worsened metabolic derangement (increased lactate-to-pyruvate ratio, reduced tissue glucose) 5